The identity and topographic location of ocular inflammatory, degenerative, and tumor cells and their products in patient specimens are analyzed by routine pathology, immunohistochemistry, in situ hybridization, microdissection and various molecular techniques including PCR, RT-PCR, and RFLP assay. The application of cutting-edge modern technology allows us to provide accurate pathological assessments of the disease, guides us in selecting an appropriate therapy for the patient, and helps us to better understand the disease mechanisms. In FY2003, we continued and accomplished the following in our research: 1. Detection of Genes and Proteins in Ocular Lymphoma Cells: We continued to detect IgH gene rearrangements and vitreal IL-10 elevations as useful adjuncts for primary intraocular B-cell lymphoma (PIOL) diagnosis. A high ratio of IL-10 to IL-6 in the vitreous was in favor of PIOL. A 1.0 cutoff rule for the ratio was correct 74.7% of the time (sensitivity 74.3%, specificity 75.0%) for the diagnosis of PIOL. 2. New Pathology and Pathogenesis of Ocular Inflammation and Other Diseases: Using microdissection and PCR, we are able to detect the Histoplasma capsulatum gene in ocular histoplasmosis syndrome, molecular monoclonality in orbital lymphoma and ocular post-transplant lymphoproliferative disorder after renal transplantation. We were the first group to report Waldenstrom macroglobulinemia-associated paraneoplastic retinopathy and the immunopathology of rapid progressive fibrovascular neovascular membrane in age-related macular degeneration. 3. Experimental Models for Various Inflammatory Ocular Diseases: We continued to investigate the role of inflammatory mediators and cytokines in the endotoxin-induced uveitis (EIU) model, a model for human anterior uveitis. We have already evaluated the effect of sex hormones on experimental autoimmune uveitis in rats. In collaboration with Drs. Caspi and Gery, several new modes and mechanisms of ocular inflammation have been discovered and published.